Thiazide Diuretics

Although thiazide diuretics are seldom used by anaesthetists, many patients scheduled for surgery are receiving these drugs for chronic hypertension or cardiac failure. There are a large number of thiazides available, all with a similar dose-response curve and diuretic effect. Bendroflumethiazide, chlorothiazide, hydrochlorothiazide and chlorthalidone are a few examples of the better known thiazide diuretics. The majority have a duration of action of 6-12 h. In comparison with loop diuretics, thiazides have a longer duration of action, act at a different site, have a low 'ceiling' effect and are less effective in renal failure.

Thiazide diuretics are administered orally, absorbed rapidly from the gastrointestinal tract and initiate a diuresis within 1-2 h. The major distinction between the available thiazides is their difference in elimination rate. They are distributed in the extracellular space and eliminated in the proximal tubule of the nephron by active secretion.

Thiazides inhibit the active pump for sodium and chloride reabsorption in the cortical ascending part of the loop of Henle and the distal convoluted tubule. Therefore, the urine-concentrating ability of the kidney is not impaired, as normally this area is responsible for less than 5% of sodium reabsorption. The diuresis achieved by the thiazides is therefore never as effective as that of the loop diuretics. It is mild but sustained. In contrast with loop diuretics, the excretion of calcium is decreased and hypercal-caemia may become a problem. In the presence of aldosterone activity, the increase in sodium delivery to the distal renal tubules is associated with increased potassium loss, similar to that of the loop diuretics. The reduced clearance of uric acid by thiazides may cause hyperuricaemia.

Thiazides are used extensively in low doses, and often combined with a low-sodium diet, for the management of essential hypertension. A reduction in extracellular fluid volume and mild peripheral vasodilatation are responsible for the sustained antihypertensive effect. The full antihypertensive effect may take up to 12 weeks to become established. Higher doses of thiazides are used for the management of congestive cardiac failure and other oedematous conditions such as nephrotic syndrome and liver cirrhosis.

The most common side-effects of the thiazides are probably dehydration and hypovolaemia. This may present as orthostatic hypotension. When administered chronically, these drugs lead typically to a diuretic-induced hypokalaemic, hypochloraemic, metabolic alkalosis. In combination with magnesium depletion, the hypokalaemia may trigger serious cardiac arrhythmias, in addition to digitalis toxicity, muscle weakness and the potentiation of non-depolarizing muscle relaxants.

Thiazides decrease the tubular secretion of urate, which may lead to a hyperuricaemia and gout. They are sulphonamide derivatives and may therefore cause inhibition of insulin release from the pancreas and blockade of peripheral glucose utilization. This may precipitate hyperglycaemia or an increase in insulin requirements in a patient with diabetes mellitus. They also lead to an increase in total blood cholesterol.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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